Bupropion; naltrexone can cause an increase in systolic and/or diastolic blood pressure as well as an increase in resting heart rate. Therefore, avoid using bupropion; naltrexone in patients with uncontrolled hypertension. Measure blood pressure and pulse prior to and at regular intervals during bupropion; naltrexone therapy, particularly among patients with controlled hypertension prior to treatment. Monitor closely during titration and the initial three months of therapy when the risk is greatest. In bupropion; naltrexone clinical trails, statistically significant increases in blood pressure and heart rate were observed in patients with and without preexisting hypertension. The clinical significance of these findings are unclear, especially in patiens with cardiovascular disease, since patients with a history of cardiac and cerebrovascular events were excluded from bupropion; naltrexone clinical trials. In clinical practice with other bupropion-containing products, hypertension, in some cases severe and requiring acute treatment, has been reported. The overall safety of bupropion; naltrexone was evaluated in 5 double-blind placebo controlled clinical trials enrolling overweight (n = 4,754) or obese patients (n = 3,239) for up to 56 weeks of treatment. All subjects received study drug in addition to diet and exercise counseling. The majority of participants received a total daily dose of 32 mg naltrexone/360 mg bupropion. Common cardiovascular adverse reactions reported in 2% or more of patients receiving bupropion; naltrexone and more frequently than placebo include: hypertension (2.4% to 3.2%) and palpitations (2.1%). Other cardiovascular related adverse reactions reported in less than 2% of patients treated with bupropion; naltrexone but with an incidence at least twice that of placebo include: sinus tachycardia and myocardial infarction. Drug-induced Brugada syndrome/pattern has also been reported during postmarketing use of bupropion-containing products.[57922]

Although not reported during clinical evaluation of bupropion; naltrexone, ocular hypertension has been reported during bupropion treatment.[40993] The pupillary dilation that occurs following the use of many antidepressant drugs including bupropion, may trigger an angle-closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.[57922]

The overall safety of bupropion; naltrexone was evaluated in 5 double-blind placebo controlled clinical trials enrolling overweight (n = 4,754) or obese patients (n = 3,239) for up to 56 weeks of treatment. All subjects received study drug in addition to diet and exercise counseling. The majority of participants received a total daily dose of 32 mg naltrexone/360 mg bupropion. During clinical trials, headache was among the most frequent adverse reactions leading to discontinuation. Dizziness was also reported to account for a number of discontinuations of treatment in clinical trials. Adverse reactions involving attention, dizziness, and syncope occurred more often in individuals randomized to bupropion; naltrexone compared to placebo (15%). Common neurological adverse reactions reported in at least 2% of patients receiving bupropion; naltrexone and more frequently than placebo included headache (17.6%), dizziness (9.9%), tremor (4%), and tinnitus (3.3%). Other neurological related adverse reactions reported in less than 2% of patients treated with bupropion; naltrexone but with an incidence at least twice that of placebo include: amnesia, balance disorder, disturbance in attention, intention tremor, lethargy, memory impairment, mental impairment, motion sickness, presyncope, and vertigo. Loss of consciousness has been reported during postmarketing use; however, frequency and causality have not been established.[57922]

Anaphylactoid reactions characterized by symptoms such as pruritus, urticaria, angioedema, and dyspnea requiring medical treatment have been reported in clinical trials with bupropion. In addition, there have been rare spontaneous postmarketing reports of erythema multiforme, Stevens-Johnson syndrome, anaphylactic shock, and drug reaction with eosinophilia and systemic symptoms (DRESS) associated with bupropion. Instruct patients to discontinue bupropion; naltrexone and consult a healthcare provider if they develop an allergic or anaphylactoid/anaphylactic reaction (e.g., skin rash, pruritus, hives, chest pain, edema, or shortness of breath) during treatment. Arthralgia, myalgia, fever with rash, and other symptoms suggestive of delayed hypersensitivity have been reported in association with bupropion. These symptoms may resemble serum sickness.[57922] The overall safety of bupropion; naltrexone was evaluated in 5 double-blind placebo controlled clinical trials enrolling overweight (n = 4,754) or obese patients (n = 3,239) for up to 56 weeks of treatment. All subjects received study drug in addition to diet and exercise counseling. The majority of participants received a total daily dose of 32 mg naltrexone/360 mg bupropion. Common dermatological adverse reactions reported in 2% or more of patients receiving bupropion; naltrexone and more frequently than placebo include: hyperhidrosis (2.6%) and rash (unspecified) (2.4%). Other skin related adverse reactions reported in less than 2% of patients treated with bupropion; naltrexone but with an incidence at least twice that of placebo include: alopecia.[57922]

The overall safety of bupropion; naltrexone was evaluated in 5 double-blind placebo controlled clinical trials enrolling overweight (n = 4,754) or obese patients (n = 3,239) for up to 56 weeks of treatment. All subjects received study drug in addition to diet and exercise counseling. The majority of participants received a total daily dose of 32 mg naltrexone/360 mg bupropion. Common phychiatric adverse reactions reported in 2% or more of patients receiving bupropion; naltrexone and more frequently than placebo include: insomnia (9.2%), anxiety (4.2%), and irritability (2.6%). Other phychiatric related adverse reactions reported in less than 2% of patients treated with bupropion; naltrexone but with an incidence at least twice that of placebo include: abnormal dreams, nervousness, dissociation (feeling spacey), tension, agitation, emotional lability. Of note, in a one-year controlled trial, patients 65 years of age and older experienced more psychiatric and sleep disorder adverse reactions in the treatment group (28.6%, n = 56) compared to placebo (6.3%, n = 32); the majority of these events were insomnia and depression.[57922] Observe patients receiving bupropion; naltrexone for the occurrence of neuropsychiatric reactions and suicidal ideation. Bupropion, when prescribed as an antidepressant or as an aid in smoking cessation, has been associated with an increased incidence of neuropsychiatric reactions including suicidal thoughts and behaviors. Antidepressant treatment can precipitate a manic, mixed, or hypomanic episode. The risk appears to be increased in patients with bipolar disorder or who have risk factors for bipolar disorder. No activation of mania or hypomania was reported in the clinical trials evaluating effects of bupropion; naltrexone in obese patients; however, patients receiving antidepressant medications and patients with a history of bipolar disorder or recent hospitalization because of psychiatric illness were excluded from bupropion; naltrexone clinical trials. When bupropion is used in smoking cessation treatment, serious neuropsychiatric symptoms including changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, aggression, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide have been reported. Although bupropion; naltrexone is not approved for these indications, screen patients for a history of bipolar disorder and the presence of risk factors for bipolar disorder (e.g., family history of bipolar disorder, suicide, or depression) prior to initiating weight-loss therapy. Instruct patients and caregivers to contact a healthcare professional if neuropsychiatric reactions occur.[57922]

The safety of bupropion; naltrexone was evaluated in 5 double-blind placebo controlled clinical trials enrolling overweight (n = 4,754) or obese patients (n = 3,239) for up to 56 weeks of treatment. All subjects received study drug in addition to diet and exercise counseling. The majority of participants received a total daily dose of 32 mg naltrexone/360 mg bupropion. During clinical trials, the most frequent adverse reactions leading to discontinuation included nausea and vomiting. Common gastrointestinal adverse reactions reported in 2% or more of patients receiving bupropion; naltrexone and more frequently than placebo include: nausea (32.5%), constipation (19.2%), vomiting (10.7%), xerostomia (8.1%), diarrhea (7.1%), upper abdominal pain (3.5%), viral gastroenteritis (3.5%), abdominal pain (2.8%), and dysgeusia (2.4%). Other GI related adverse reactions reported in less than 2% of patients treated with bupropion; naltrexone but with an incidence at least twice that of placebo include: lower abdominal pain, eructation, lip swelling, hematochezia, hernia, and cholecystitis.[57922]

The safety of bupropion; naltrexone was evaluated in 5 double-blind placebo controlled clinical trials enrolling overweight (n = 4,754) or obese patients (n = 3,239) for up to 56 weeks of treatment. All subjects received study drug in addition to diet and exercise counseling. The majority of participants received a total daily dose of 32 mg naltrexone/360 mg bupropion. Common adverse reactions reported in 2% or more of patients receiving bupropion; naltrexone and more frequently than placebo include: hot flashes (4.2%), fatigue (4%), influenza (3.4%), urinary tract infection (3.3%), and muscle cramps / strains (2.2%). Other adverse reactions reported in less than 2% of patients treated with bupropion; naltrexone but with an incidence at least twice that of placebo include: asthenia, decreased hematocrit, dehydration, feeling abnormal, feeling hot, feeling jittery, impotence (erectile dysfunction), increased blood creatinine, intervertebral disc protrusion, jaw pain, kidney infection, menstrual irregularity, polydipsia, pneumonia, staphylococcal infection, urinary urgency, vaginal bleeding, and vulvovaginal dryness.[57922] In addition, in one-year controlled trials of bupropion; naltrexone, larger mean increases in serum creatinine from baseline to trial endpoint were observed in the treatment group compared with the placebo group. Malaise has been reported during postmarketing use; however, frequency and causality have not been established.[57922]

Although not reported during clinical evaluation of bupropion; naltrexone, cases of hepatitis and clinically significant liver dysfunction were observed in association with naltrexone exposure during naltrexone clinical trials and in post-marketing reports for patients using naltrexone. Warn patients of the risk of hepatic injury and advised them to seek medical attention if they experience symptoms of acute hepatitis. Discontinue treatment with bupropion; naltrexone in the event of symptoms and/or signs of acute hepatitis. Transient, asymptomatic hepatic transaminase elevations have also been observed with naltrexone use; however, cases were often reported in patients with other potential contributory factors. In bupropion; naltrexone clinical trials, there were no cases of elevated transaminases greater than three times the upper limit of normal (ULN) in conjunction with an increase in bilirubin greater than two times ULN. Elevated hepatic enzymes were reported among less than 2% of bupropion; naltrexone treated patients but with an incidence at least twice that of placebo.[57922]

Bupropion, a component of bupropion; naltrexone, is known to cause seizures in a dose dependent fashion. Avoid use of bupropion; naltrexone in patients at high risk for seizures and follow dosing recommendations closely in order to minimize the risk of bupropion induced seizures. If a patient experiences a seizure while on treatment, discontinue bupropion; naltrexone and do not restart. In clinical evaluation of bupropion; naltrexone, seizure was reported in 0.1% and 0% of patients receiving bupropion; naltrexone and placebo, respectively. Bupropion may cause amphetamine-like effects and therefore has been studied in patients with a history of substance abuse. Results from single-dose studies suggest that the recommended daily dose of bupropion when administered in divided doses is not likely to be significantly reinforcing to amphetamine or CNS stimulant abusers. However, because clinical trial results may not reliably predict the abuse potential of drugs, the benefits of treatment should be weighed against the potential for abuse prior to administering bupropion; naltrexone to patients with a history of substance abuse. The inhalation of crushed bupropion tablets or injection of dissolved bupropion has resulted in seizures and/or cases of death.[57922]

The concurrent administration of monoamine oxidase inhibitor therapy (MAOI therapy) during bupropion; naltrexone is contraindicated. At least 14 days should elapse between the discontinuation of an MAOI and initiation of bupropion; naltrexone treatment. Conversely, at least 14 days should be allowed after stopping bupropion; naltrexone before starting an MAOI.[57922] There is an increased risk of hypertensive reactions when bupropion is used concurrently with other drugs that inhibit the reuptake of dopamine or norepinephrine or inhibit their metabolism such as MAOIs. Starting bupropion; naltrexone in a patient treated with reversible MAOIs such as linezolid or intravenous methylene blue is also contraindicated. Clinicians are advised to carefully review the potential for drug-drug interactions prior to prescribing bupropion; naltrexone.[57922]

Bupropion; naltrexone is contraindicated for use in patients with uncontrolled hypertension; use this product cautiously in patients with controlled hypertension. Bupropion; naltrexone is known to cause an increase in systolic and diastolic blood pressure as well as an increase in resting heart rate. Hypertension, in some cases severe and requiring acute treatment, has been reported with bupropion therapy for various indications in clinical practice. Monitor blood pressure and pulse before and at regular intervals during therapy, particularly among patients with controlled hypertension before treatment. Monitor closely during titration and the initial 3 months of therapy when the risk is highest.[57922] Use with caution and with appropriate monitoring of blood pressure, heart rate, and rhythm in patients with existing cardiac disease or cerebrovascular disease. Patients with cardiac disease or cerebrovascular disease, including patients with a history of acute myocardial infarction, myocardial infarction (MI) or cerebrovascular accident (CVA) in the previous 6 months, life-threatening cardiac arrhythmias, or heart failure were excluded from bupropion; naltrexone clinical trials and, thus, should only receive this product for weight management with careful consideration of risks and benefits and close monitoring.[57922] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, avoid bupropion; naltrexone in obese patients with existing hypertension if other weight loss medications are appropriate because weight loss assisted by bupropion; naltrexone cannot be expected to reduce blood pressure, and the product is contraindicated in uncontrolled hypertension. Bupropion; naltrexone is not a preferred weight loss medication in patients with established coronary artery disease (CAD) or history or risk of cardiac arrhythmias, but is reasonable to use with caution if weight loss goals are met, with careful monitoring of blood pressure, heart rate, and rhythm. Data are insufficient regarding the benefits of the use of bupropion; naltrexone in obese patients with heart failure; the AACE/ACE Obesity Guidelines recommend avoidance until more data are available.[62881]

Bupropion; naltrexone use is contraindicated in patients with a seizure disorder, a history of seizures, and in patients undergoing abrupt benzodiazepine withdrawal, as well as abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs because the seizure risk is increased. Bupropion, a component of bupropion; naltrexone, is known to cause seizures in a dose-dependent fashion. Consider any other patient factors, clinical situations, and concomitant medications that may lower the seizure threshold before initiating treatment with bupropion; naltrexone. In particular, use bupropion; naltrexone with caution in patients with a history of head trauma, severe stroke, arteriovenous malformation, central nervous system (CNS) tumor (brain tumor) or CNS infection (e.g., meningitis), metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, and hypoxemia), substance abuse (e.g., alcoholism or excessive use of alcohol or sedatives), addiction to cocaine or stimulants, or withdrawal from sedatives), patients with diabetes treated with insulin and/or oral diabetic medications (sulfonylureas and meglitinides) that may cause hypoglycemia, and during concomitant administration of medications that may lower the seizure threshold, including other bupropion products, antipsychotics, tricyclic antidepressants, theophylline, or systemic steroids.[57922] Clinical experience suggests that the risk of seizures may be minimized by adhering to the dosing recommendations set forth for bupropion; naltrexone, including the following: a maximum daily bupropion dose of 360 mg/day (i.e., four tablets/day), administering the total daily dose in divided doses (twice daily), gradually titrating dose, taking no more than 2 tablets at any one time, avoiding administration with high-fat meals, and if a dose is missed, advising the patient to wait until the next scheduled dose to resume the regular dosing schedule. If a patient experiences a seizure while undergoing weight loss treatment with bupropion; naltrexone, discontinue therapy and do not restart.[57922] Bupropion may cause amphetamine-like effects and therefore has been studied in patients with a history of substance abuse. Results from single-dose studies suggest that the recommended daily dose of bupropion when administered in divided doses is not likely to be significantly reinforcing to amphetamine or CNS stimulant abusers. Bupropion; naltrexone has not been formally studied for abuse potential, tolerance, or physical dependence. In outpatient clinical studies of up to 56 weeks, there was no evidence of euphoria, physical dependence, diversion, or abuse, or an abstinence syndrome following either abrupt or tapered drug discontinuation. Naltrexone is a pure opiate antagonist and does not lead to physical or psychological dependence. Weigh the benefits of obesity treatment against the potential for abuse before using bupropion; naltrexone in those with a history of substance abuse. Bupropion; naltrexone extended-release tablets are intended for oral use only; the inhalation of crushed bupropion tablets or injection of dissolved bupropion has resulted in seizures and cases of death.[57922] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, bupropion; naltrexone should be avoided in obese patients with alcoholism or substance abuse due to the seizure risk with bupropion which may increase the likelihood of seizures during alcohol or other medication withdrawal. The AACE/ACE Obesity Guidelines recommend that other weight loss medications be considered in patients with a substance abuse disorder.[62881]

Bupropion; naltrexone use is contraindicated in patients with a current diagnosis or previous history of bulimia nervosa or anorexia nervosa because the risk for seizure is known to be increased in these patients.[57922] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, bupropion; naltrexone should be avoided in patients with eating disorders that involve purging or bulimia nervosa. Patients with bulimia may be susceptible to seizures due to metabolic imbalance or other risk factors. There are insufficient data on the use of bupropion; naltrexone in overweight or obese patients with binge eating disorder (BED), but there is a possible benefit based on studies with bupropion. According to the AACE/ACE Obesity Guidelines, there are insufficient data on the benefits of the use of bupropion; naltrexone following bariatric surgery.[62881]

Bupropion; naltrexone contains naltrexone, an opioid receptor antagonist. Bupropion; naltrexone is contraindicated in patients who require chronic opioid therapy, in patients experiencing acute opioid withdrawal, and in patients receiving an opiate agonist (e.g., methadone, tramadol, and many others) or partial agonist (e.g., buprenorphine). If chronic opioid therapy is required, bupropion; naltrexone treatment should be stopped. To prevent the occurrence of either precipitated opioid withdrawal or exacerbation of pre-existing subclinical withdrawal symptoms, opioid-dependent patients, including those being treated for alcohol dependence, should be opioid-free before starting bupropion; naltrexone treatment.[57922] An opioid-free interval of a minimum of 7 to 10 days is recommended for patients previously dependent on short-acting opioids; patients transitioning from buprenorphine or methadone may need as long as 2 weeks. Patients should be made aware of the risks associated with precipitated opioid withdrawal and encouraged to give an accurate account of last opioid use. In patients requiring intermittent opioid treatment, bupropion; naltrexone therapy should be temporarily discontinued, and lower doses of opioids may be needed. Even at lower opioid doses, patients may still experience increased sensitivity to opioid actions and adverse effects after bupropion; naltrexone treatment is discontinued. Advise patients of the serious consequences of trying to overcome the opioid blockade which may lead to a fatal overdose or life-threatening opioid intoxication (e.g., respiratory arrest, circulatory collapse).[57922]

Bupropion; naltrexone therapy for weight management has not been studied in clinical trials and is not recommended in children and adolescents less than 18 years old; safety and efficacy have not been established.[57922] Use of agents for weight loss off-label in properly selected older children or adolescents is recommended to be within the context of appropriate clinical trials.[58571] The bupropion component of bupropion; naltrexone is used for the treatment of major depressive disorder (MDD) and smoking cessation; therefore, precautions about these bupropion products should be considered when treating patients with bupropion; naltrexone. All patients being treated with an antidepressant for any indication should be monitored and observed for the emergence of anxiety, agitation, irritability, unusual changes in behavior, or suicidality, and to report such symptoms immediately to healthcare providers. All antidepressants include a boxed warning detailing the risk of suicide in pediatric patients. The risk of suicidality for these drugs was identified in a pooled analysis of 24 placebo-controlled trials (n = 4,400) lasting up to 16 weeks in pediatric patients with major depressive disorder (MDD), obsessive-compulsive disorder (OCD), or other psychiatric disorders. The analysis showed a greater risk of suicidality during the first few months of treatment in those receiving antidepressants. Pooled analysis of short-term clinical trials during early phase treatment with antidepressants in young adults (18 to 24 years) also showed an increased risk of suicidal thinking and behavioral changes. No suicides occurred in any of the pediatric antidepressant trials. It is unknown if the suicidality risk in children and young adults extends to longer-term therapy. In placebo-controlled trials with bupropion; naltrexone (equivalent to bupropion doses of 360 mg/day) for the treatment of obesity in adults, no suicides or suicide attempts were reported in studies up to 56 weeks duration. In these same studies, suicidal ideation was reported in 0.2% of patients treated with placebo compared with 0.03% of those treated with bupropion; naltrexone. Bupropion; naltrexone should be prescribed in the smallest quantity consistent with good patient management to reduce the risk of overdose.[57922]

Serious neuropsychiatric adverse events have been reported in patients taking bupropion for various indications. Patients should be observed for a potential psychiatric event or worsening of pre-existing psychiatric illness (e.g., schizophrenia, depression, bipolar disorder) during treatment with bupropion; naltrexone. Antidepressants have been associated with the development of mania or hypomania in susceptible individuals, such as those with bipolar disorder or who have risk factors for bipolar disorder. Patients should be adequately screened for bipolar disorder and risk factors for bipolar disorder before initiating bupropion; naltrexone. No activation of mania or hypomania was reported in the clinical trials evaluating the effects of bupropion; naltrexone in obese patients; however, patients receiving other antidepressants or with a history of bipolar disorder or recent hospitalization because of psychiatric illness were excluded from the bupropion; naltrexone clinical weight loss trials. Postmarketing reports during use of bupropion products have included mood or behavioral changes (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, panic, suicidal ideation, suicide attempt, and completed suicide in patients with and without a psychiatric history. Advise patients and caregivers that the patient should stop taking bupropion; naltrexone and contact a healthcare provider immediately if agitation, depressed mood, suicidal ideation, suicidal behavior, or other behavioral changes that are not typical for the patient are observed. Depression, suicide, attempted suicide, and suicidal ideation has been reported during postmarketing use of naltrexone in the treatment of opioid dependence, although no causal relationship has been observed.[57922] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, there are insufficient safety data on the use of bupropion; naltrexone in obese patients with depression or other mood disorders. Use with caution and avoid bupropion; naltrexone in adolescents and young adults and those patients taking medication for depression. All patients undergoing weight loss therapy should be monitored for mood disorders, depression, and suicidal ideation. Evidence assessing safety and efficacy of weight loss medications in patients with a psychotic disorder (e.g., schizophrenia) is insufficient, and use of bupropion; naltrexone should be avoided. The AACE/ACE Obesity Clinical Guidelines suggest that patients receiving an antipsychotic be treated with structured lifestyle modifications to promote weight loss and weight gain prevention; metformin may be beneficial for modest weight loss and metabolic improvements in patients receiving an antipsychotic.[62881]

Maximum recommended daily maintenance doses of bupropion; naltrexone are reduced in patients with moderate hepatic disease. Avoid use of this product in patients with severe hepatic disease. In a pharmacokinetic study of bupropion; naltrexone in subjects with hepatic impairment (mild, moderate, and severe) compared to normal controls, exposures to naltrexone, bupropion, and their metabolites were increased. Naltrexone as a single agent has been associated with transient, asymptomatic hepatic transaminase elevations as well as cases of hepatotoxicity, hepatitis, and other forms of significant liver dysfunction, although potential causative or contributory etiologies have often been identified, including pre-existing alcoholic liver disease, hepatitis B and/or C infection, and concomitant usage of other potentially hepatotoxic drugs. Warn patients of the risk of hepatic injury and advise them to seek medical attention if they experience symptoms of acute hepatitis. Discontinue treatment in the event of symptoms and/or signs of acute hepatitis. Close monitoring for cholelithiasis or pancreatitis is recommended in all obese patients, regardless of treatment, due to a proven association between obesity and these conditions.[57922] [62881]

Caution is recommended when prescribing bupropion; naltrexone to patients with closed-angle glaucoma. The pupillary dilation that can occur with antidepressants may precipitate a closed-angle glaucoma attack in patients with anatomically narrow angles who do not have a patent iridectomy. An acute attack of closed-angle glaucoma is considered a medical emergency because the increased intraocular pressure is rapid and severe, and may quickly result in blindness if left untreated.[57922] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, other weight loss medications (i.e., orlistat, lorcaserin, or liraglutide) are preferred treatment options for patients with glaucoma and bupropion; naltrexone should be avoided if possible since the drug may trigger an acute attack of closed-angle glaucoma.[62881]

Weight loss may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus (T2DM) treated with insulin and/or insulin secretagogues (e.g., sulfonylureas). Monitor blood glucose levels before starting bupropion; naltrexone and during treatment. Decreases in medication doses for antidiabetic medications which are non-glucose-dependent should be considered to mitigate the risk of hypoglycemia. If a patient develops hypoglycemia after starting bupropion; naltrexone, appropriate changes should be made to the antidiabetic drug regimen. If a patient develops hypoglycemia after starting bupropion; naltrexone, appropriate changes should be made to the antidiabetic drug regimen.[57922] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, weight loss medications should be considered as an adjunct to lifestyle therapy in all patients with T2DM as needed for weight loss sufficient to improve glycemic control, lipids, and blood pressure. There are insufficient data to determine if bupropion; naltrexone prevents progression to T2DM in obese patients. In controlled trials of other prescribed weight loss medications (i.e., orlistat, phentermine; topiramate, or liraglutide) as an adjunct to lifestyle therapy versus lifestyle therapy alone for diabetes prevention, a greater weight loss and more profound reductions in incident diabetes occurred in the medication plus lifestyle therapy groups[62881]

No dosage adjustments of bupropion; naltrexone are required in patients with mild renal impairment. Due to an increase in exposure of naltrexone and metabolites of bupropion, maximum dosages of bupropion; naltrexone are recommended to be reduced in patients with moderate to severe renal impairment. Bupropion; naltrexone is not recommended for use in patients with end-stage renal disease (i.e., renal failure or ESRD on dialysis).[57922] The American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines state to avoid this product in patients with a CrCl less than 30 mL/minute. Bupropion; naltrexone is a preferred weight loss medication in patients with a history of or at risk for nephrolithiasis, as this product does not increase the risk for renal stones.[62881]

Use caution when prescribing bupropion; naltrexone to geriatric patients. Clinical studies for obesity did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects; no patients in clinical trials were over the age of 75 years. Older patients may be more sensitive to the central nervous system (CNS) adverse effects of bupropion; naltrexone. The drug components are renally excreted and the risk of adverse reactions are greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.[57922] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, there are insufficient data on the use of bupropion; naltrexone for weight reduction in elderly obese patients and additional studies are needed to assess safety and efficacy. Elderly patients selected for weight loss therapy should have structured lifestyle interventions including reduced calorie meal plans and exercise, clear health-related goals including blood pressure reduction, diabetes prevention in high risk patients with pre-diabetes, and improvements in osteoarthritis, mobility, and physical functioning. Overweight or obese elderly patients being considered for a weight loss medication should be evaluated for osteopenia and sarcopenia.[62881]

Weight loss offers no benefit during pregnancy and may result in fetal harm; therefore, if pregnancy occurs during the use of bupropion; naltrexone, the patient should be apprised of the risk to the fetus and the drug should be discontinued. Available data from the individual components of bupropion; naltrexone use in pregnant patients have not demonstrated a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, a minimum weight gain, and no weight loss, is currently recommended for all pregnant women, including those who are already overweight or obese, due to the obligatory weight gain that occurs in maternal tissues during pregnancy. According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, weight loss medications must not be used during pregnancy. The AACE/ACE Obesity Guidelines recommend contraception requirements. Women of childbearing potential receiving bupropion; naltrexone should use contraception and discontinue the drug if pregnancy occurs. There is no known indication for the use of obesity drugs in infants; the effect on infants or neonates exposed in utero is uncertain; drug-related withdrawal syndromes have been reported postpartum from the maternal use of antidepressant category drugs of other types during pregnancy.[57922] [62881]

The developmental and health benefits of breast-feeding should be considered along with the clinical need for bupropion; naltrexone to the mother and any potential adverse effects on the breastfed infant from the drug or from the underlying condition of the mother. Bupropion and its metabolites are excreted in human milk. Transfer of naltrexone and 6-beta-naltrexol into human milk has been reported with oral naltrexone. There are no data on bupropion; naltrexone or their metabolites on milk production. In 1 small lactation study (n = 10) of bupropion, the average daily infant exposure (assuming 150 mL/kg daily consumption) to bupropion and its active metabolites was 2% of the maternal weight-adjusted dose. Postmarketing reports have described seizures in breastfed infants exposed to bupropion through breast milk; however, causality has not been established. According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, weight-loss medications should not be used in women who are lactating and breast-feeding.[57922] [62881]

Laboratory test interference has been reported with bupropion use. False-positive urine immunoassay screening tests for amphetamines have been reported in patients taking bupropion. The false-positive result is due to lack of specificity of some screening tests. False-positive test results may result even following discontinuation of bupropion therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish bupropion from amphetamines.[57922]